Nervous system effects in rats on subacute exposure by lead-containing nanoparticles via the airways

Context and objective: Lead (Pb) is a heavy metal harmful for human health and environment. From leaded gasoline (still used in certain countries), and in Pb processing and reprocessing industries, airborne particles are emitted which can be inhaled. In such exposure, the size of particles entering the airways is crucial. The nervous system is a primary target for Pb, and consequences like occupational neuropathy and delayed mental development of children are well-known. The aim of this work was to investigate the neurotoxicity of Pb nanoparticles (NPs) applied into the airways of rats. Methods: Nano-sized lead oxide particles (mean diameter ca. 20 nm) were suspended in distilled water and instilled into the trachea of adult male Wistar rats (in doses equivalent to 2 and 4 mg/kg Pb), 5 times a week for 3 and 6 weeks. At the end, open field motility was tested, then central and peripheral nervous activity was recorded in urethane anesthesia. Results and conclusion: The treated rats’ body weight gain was significantly lower than that of the controls from the 3rd week onwards, and the weight of their lungs was significantly increased. Horizontal motility increased while vertical motility decreased. Spontaneous cortical activity was shifted to higher frequencies. The somatosensory cortical evoked potential showed increased latency and decreased frequency-following ability, and similar alterations were seen in the tail nerve. Significant Pb deposition was measured in blood, brain, lung and liver samples of the treated rats. The experiments performed seem to constitute an adequate model of the human effects of inhaled Pb NPs.

[1]  A. Herz,et al.  Pharmacologically induced alterations of cortical and subcortical evoked potentials compared with physiological changes during the awake-sleep cycle in cats. , 1967, Electroencephalography and clinical neurophysiology.

[2]  A. Eklund,et al.  Dissolution of metals by human and rabbit alveolar macrophages. , 1985, British journal of industrial medicine.

[3]  K. Murata,et al.  Subclinical neurophysiological effects of lead: A review on peripheral, central, and autonomic nervous system effects in lead workers. , 2000, American journal of industrial medicine.

[4]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[5]  H. Coffigny,et al.  Effects of Lead Poisoning of Rats During Pregnancy on the Reproductive System and Fertility of their Offspring , 1994, Human & experimental toxicology.

[6]  D. Holtzman,et al.  The pathogenesis of lead encephalopathy , 1980, Virchows Archiv A.

[7]  D. Rasmusson,et al.  Cortical acetylcholine release and electroencephalogram activation evoked by ionotropic glutamate receptor agonists in the rat basal forebrain , 2004, Neuroscience.

[8]  P. Sundgren,et al.  Magnetic resonance spectroscopy. , 2005, Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society.

[9]  A. Kurunczi,et al.  Behavioral effects of subchronic inorganic manganese exposure in rats. , 2007, American journal of industrial medicine.

[10]  J. Thomas,et al.  The pathogenesis of lead encephalopathy. , 1974, The Indian journal of medical research.

[11]  S. Rothenberg,et al.  Spatial distribution of EEG theta activity as a function of lifetime lead exposure in 9-year-old children. , 2001, Neurotoxicology.

[12]  V. Benignus,et al.  Effects of age and body lead burden on CNS function in young children. II. EEG spectra. , 1981, Electroencephalography and clinical neurophysiology.

[13]  T. B. Griffin,et al.  Clinical studies on men continuously exposed to airborne particulate lead. , 1975, Environmental quality and safety. Supplement.

[14]  R. Deane,et al.  Permeability of the blood-brain barrier to lead. , 1993, Neurotoxicology.

[15]  L. Strużyńska,et al.  The role of astroglia in Pb-exposed adult rat brain with respect to glutamate toxicity. , 2005, Toxicology.

[16]  G. P. Smith,et al.  Mesolimbic and mesocortical dopaminergic neurons are necessary for normal exploratory behavior in rats , 1980, Neuroscience Letters.

[17]  K. A. Kooi,et al.  The evoked potentials: W. Cobb and C. Morocutti (Editors). (Electroenceph. clin. Neurophysiol., Suppl. No. 26, Elsevier, Amsterdam, New York, 1968, 218 p., Dfl. 62.50, U.S. $22.50) , 1969 .

[18]  K. Murata,et al.  Subclinical cerebellar anterior lobe, vestibulocerebellar and spinocerebellar afferent effects in young female lead workers in China: computerized posturography with sway frequency analysis and brainstem auditory evoked potentials. , 2002, Industrial health.

[19]  P. Gavazzo,et al.  Molecular determinants of Pb2+ interaction with NMDA receptor channels , 2008, Neurochemistry International.

[20]  J. Mandel,et al.  Neurobehavioural testing in workers occupationally exposed to lead: systematic review and meta-analysis of publications , 2002, Occupational and environmental medicine.

[21]  C. Ong,et al.  Neurophysiological studies on workers exposed to lead. , 1985, British journal of industrial medicine.

[22]  I. Ho,et al.  Effects of chronic lead (Pb) exposure on neurobehavioral function and dopaminergic neurotransmitter receptors in rats. , 1999, Toxicology letters.

[23]  J. Coyle,et al.  Oxidative stress, glutamate, and neurodegenerative disorders. , 1993, Science.

[24]  P. Gluckman,et al.  Neuroprotective strategies for basal ganglia degeneration: Parkinson’s and Huntington’s diseases , 2000, Progress in Neurobiology.

[25]  G. Paxinos The Rat nervous system , 1985 .

[26]  P. Waite,et al.  Trigeminal sensory system. , 2012 .

[27]  Joseph P Huston,et al.  Behavioral phenotyping of the MPTP mouse model of Parkinson's disease , 2001, Behavioural Brain Research.

[28]  D. Kleinbaum,et al.  5-year follow-up study of children with low-to-moderate lead absorption: electrophysiological evaluation. , 1985, Environmental Research.

[29]  Wei Li,et al.  Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO(2) nanoparticles. , 2008, Toxicology.

[30]  N. Schork,et al.  Ventilation and metabolism among rat strains. , 1997, Journal of applied physiology.

[31]  Y. H. Chang,et al.  Effect of heat treatment and Co on the giant magnetoresistance of Fe-60 Cr–XCo alloy thin films , 1997 .

[32]  K. Schärer The effect of chronic underfeeding on organ weights of rats. How to interpret organ weight changes in cases of marked growth retardation in toxicity tests? , 1977, Toxicology.

[33]  P. Waite,et al.  CHAPTER 26 – Trigeminal Sensory System , 2004 .

[34]  Wei Zheng,et al.  Evidence for altered hippocampal volume and brain metabolites in workers occupationally exposed to lead: a study by magnetic resonance imaging and (1)H magnetic resonance spectroscopy. , 2008, Toxicology letters.

[35]  P. Oteiza,et al.  Lead intoxication: antioxidant defenses and oxidative damage in rat brain. , 1999, Toxicology.

[36]  Z. Kónya,et al.  Metal deposition and functional neurotoxicity in rats after 3-6 weeks nasal exposure by two physicochemical forms of manganese. , 2010, Environmental toxicology and pharmacology.

[37]  G. Goldstein,et al.  Pathogenesis of lead encephalopathy. Uptake of lead and reaction of brain capillaries. , 1974, Archives of neurology.

[38]  D. Taylor,et al.  Human Respiratory Tract Model for Radiological Protection , 1996 .

[39]  K. Savolainen,et al.  Lead amplifies glutamate-induced oxidative stress. , 1995, Free radical biology & medicine.

[40]  T. Narahashi,et al.  Potent blocking action of lead on voltage-activated calcium channels in human neuroblastoma cells SH-SY5Y , 1991, Brain Research.

[41]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[42]  A. Kurunczi,et al.  Behavioral and neurotoxic effects seen during and after subchronic exposure of rats to organic mercury. , 2005, Environmental toxicology and pharmacology.

[43]  N. Miyai,et al.  Occupational health education and collaboration for reducing the risk of lead poisoning of workers in a battery manufacturing plant in Thailand. , 2004, Industrial health.

[44]  Lars Järup,et al.  Hazards of heavy metal contamination. , 2003, British medical bulletin.

[45]  H. Coffigny,et al.  Effect of Ingestion and Inhalation of Lead on the Reproductive System and Fertility of Adult Male Rats and their Progeny , 1993, Human & experimental toxicology.

[46]  J. Suszkiw Presynaptic disruption of transmitter release by lead. , 2004, Neurotoxicology.

[47]  W. Kreyling,et al.  Ultrafine particle-lung interactions: does size matter? , 2006, Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine.